Use this site to develop the concepts surrounding autocoid & antihistamines drugs and their mechanism of action
Autocoids:
· Comes from the Greek words "autos" (self) and "akos" (cure) · Naturally occuring and nonspecific substances · Examples include: amines (histamine), polypeptides (angiotensin, bradykinin, kallidin), and lipid-derived substances (prostaglandins, leukotrienes, and platelet-activating factor) · Histamine was the first autocoid to be discovered
Histamines
Histamines are found most in tissues in the mast cell and in blood in basophils and are released by degranulation. Highest in concentrations: in the lungs, skin, and intestinal mucosa. Lowest concentrations: in the pancreas, spleen, liver, and kidney.
Stimuli Triggering the Release:
Tissue Injury
Allergic Reactions
Drugs and other Foreign Compounds
Metabolism - inactivated by methylation of the imidazole ring by the enzyme histamine-N-methyltransferase or oxidative deamination of histamine by diamine oxidase to produce imidazole acetic acid, much of which is subsequently conjugated with ribose.
Pharmacologic Effects - Histamine causes the relaxation of vascular smooth muscle in smaller blood vessels, constriction of some larger blood vessels, stimulation of exocrine glands, especially those of the gastric mucosa. There are three histamine receptors (G protein-linked):
H1 Receptors - mediate effects on smooth muscle, leading to vasodilation, increased vascular permeability, and contraction of nonvascular smooth muscle.
H2 Receptors - mediate stimulation of gastric acid secretion and may be involved in other effects, such as the direct cardiac stimulation and vasodilation seen after high doses of antihistamine.
H3 Receptors - the function has not yet been established, but appear to antagonize stimulatory effects mediated by the activation of H1 receptors. Inhibits the release of norepinephrine.
Cardiovascular system(H2 mostly)- dilation of terminal arterioles, capillaries, and postcapillary venules and leads to a sharp decrease in peripheral resistance and a consequent fall in blood pressure. Cutaneous flushing, over the face and upper trunk, and a rise in skin temperature. Circulatory depression is predominate. Nonvascular smooth muscle-the smooth muscle, bronchioles and gastrointestinal tract is most sensitive to this action. People with asthma are highly susceptible to histamine. Exocrine glands- Histamine plays a major role in the physiological role in gastric secretion. Although histamine can enhance salivary and lacrimal gland secretion, this effect is minimal unless large doses are used.
General Therapeutic Uses - There are no valid therapeutic applications but could be used as a diagnostic tool the assessment of gastric acid production.
Adverse Effects - Effects are dose dependent, cutaneous flushing, hypotension, headache, visual disturbances, dyspnea, and gastrointestinal disturbances such as nausea, vomiting, and diarrhea. Massive dosages may lead to shock and circulatory failure.
Antihistamines̶ describe the: (H1, H2, H3, receptor antagonist) Pharmacologic effects – H1 antihistamines-can inhibit the contraction GI and bronchial smooth muscle. They antagonize the increase secretions of the salivary and lacrimal glands and the increase release of epinephrine. they appear to interact with the H1 receptors on the target cell, resulting in a decreased availabilityof these receptors for histamine (this can be reversed with increased concentration of histamine). Adverse reactions – CNC depressant manifested by as drowsiness, lethargy, and decrease motor coordination. Ethanolamines and phenothiazines are the most sedative. GI distrurbances-nausea, vomiting, epigastric distress. P.373 Toxicity – large doses can cause marked stimulation of CNS manifestations by hallucinations, excitement, Uses – (H1):allergic conditions, they are most effective when given before the release of histamine.
H1 antihistamines: 1.Nasal allergies. They relieve rihnorrhea, sneezing, lacrimation, itching of the eyes and nasal mucosa.
2. Acute and chronic urticaria. They are topically effective in treating pruritus and uticaria which can cause allergic dermatitis.
3. Epinephrine used for severe anaphylactic reaction. Antihistamines may be given after emergency is controlled.
4. Anti-motion sickness.
5. OTC sold as hypnotics that include H1 because of their sedative effect.
6. Reduction of tremors, muscle rigidity, headaches…….
Use in dentistry: H1-Promethazine, hydroxyzine, and diphenhydraminez may be used in conscious sedation as premedication for deep sedation. H1 antihistamines can also reduce postoperative nausea and vomiting.
Adverse effectsH1- disturbances in cardiac rhythm, hallucinations, excitement, tremors, and convulsions. Allergic reactions include urticarial, bullous, or petechial rashes.
H2 antihistamines:
Effects- cause a marked reduction in H+ output, pepsin activity, and the total volume of gastric secretion.
Uses of H2: inhibit both basal and stimulate secretion of gastric acid. Used on Gi disorders to relieve reduction of acid secretion may relieve symptoms.
Adverse effects H2- minor symptoms: dizziness, lethargy, and fatigue. More serious- mental confusion, delirium, seizures. Cimetidine has been shown to increase blood concentrations of numerous drugs, including anticoagulation of the warfarin type, TCAs, and various benzodiazepines.
Use this site to develop the concepts surrounding autocoid & antihistamines drugs and their mechanism of action
Autocoids:
· Comes from the Greek words "autos" (self) and "akos" (cure)· Naturally occuring and nonspecific substances
· Examples include: amines (histamine), polypeptides (angiotensin, bradykinin, kallidin), and lipid-derived substances (prostaglandins, leukotrienes, and platelet-activating factor)
· Histamine was the first autocoid to be discovered
Histamines
Histamines are found most in tissues in the mast cell and in blood in basophils and are released by degranulation.Highest in concentrations: in the lungs, skin, and intestinal mucosa.
Lowest concentrations: in the pancreas, spleen, liver, and kidney.
Stimuli Triggering the Release:
Metabolism - inactivated by methylation of the imidazole ring by the enzyme histamine-N-methyltransferase or oxidative deamination of histamine by diamine oxidase to produce imidazole acetic acid, much of which is subsequently conjugated with ribose.
Pharmacologic Effects - Histamine causes the relaxation of vascular smooth muscle in smaller blood vessels, constriction of some larger blood vessels, stimulation of exocrine glands, especially those of the gastric mucosa. There are three histamine receptors (G protein-linked):
- H1 Receptors - mediate effects on smooth muscle, leading to vasodilation, increased vascular permeability, and contraction of nonvascular smooth muscle.
- H2 Receptors - mediate stimulation of gastric acid secretion and may be involved in other effects, such as the direct cardiac stimulation and vasodilation seen after high doses of antihistamine.
- H3 Receptors - the function has not yet been established, but appear to antagonize stimulatory effects mediated by the activation of H1 receptors. Inhibits the release of norepinephrine.
Cardiovascular system(H2 mostly)- dilation of terminal arterioles, capillaries, and postcapillary venules and leads to a sharp decrease in peripheral resistance and a consequent fall in blood pressure. Cutaneous flushing, over the face and upper trunk, and a rise in skin temperature. Circulatory depression is predominate.Nonvascular smooth muscle-the smooth muscle, bronchioles and gastrointestinal tract is most sensitive to this action. People with asthma are highly susceptible to histamine.
Exocrine glands- Histamine plays a major role in the physiological role in gastric secretion. Although histamine can enhance salivary and lacrimal gland secretion, this effect is minimal unless large doses are used.
General Therapeutic Uses - There are no valid therapeutic applications but could be used as a diagnostic tool the assessment of gastric acid production.
Adverse Effects - Effects are dose dependent, cutaneous flushing, hypotension, headache, visual disturbances, dyspnea, and gastrointestinal disturbances such as nausea, vomiting, and diarrhea. Massive dosages may lead to shock and circulatory failure.
Antihistamines ̶ describe the: (H1, H2, H3, receptor antagonist)
Pharmacologic effects – H1 antihistamines-can inhibit the contraction GI and bronchial smooth muscle. They antagonize the increase secretions of the salivary and lacrimal glands and the increase release of epinephrine. they appear to interact with the H1 receptors on the target cell, resulting in a decreased availabilityof these receptors for histamine (this can be reversed with increased concentration of histamine).
Adverse reactions – CNC depressant manifested by as drowsiness, lethargy, and decrease motor coordination. Ethanolamines and phenothiazines are the most sedative. GI distrurbances-nausea, vomiting, epigastric distress. P.373
Toxicity – large doses can cause marked stimulation of CNS manifestations by hallucinations, excitement,
Uses – (H1):allergic conditions, they are most effective when given before the release of histamine.
H1 antihistamines:
1. Nasal allergies. They relieve rihnorrhea, sneezing, lacrimation, itching of the eyes and nasal mucosa.
2. Acute and chronic urticaria. They are topically effective in treating pruritus and uticaria which can cause allergic dermatitis.
3. Epinephrine used for severe anaphylactic reaction. Antihistamines may be given after emergency is controlled.
4. Anti-motion sickness.
5. OTC sold as hypnotics that include H1 because of their sedative effect.
6. Reduction of tremors, muscle rigidity, headaches…….
Use in dentistry: H1-Promethazine, hydroxyzine, and diphenhydraminez may be used in conscious sedation as premedication for deep sedation. H1 antihistamines can also reduce postoperative nausea and vomiting.
Adverse effects H1- disturbances in cardiac rhythm, hallucinations, excitement, tremors, and convulsions. Allergic reactions include urticarial, bullous, or petechial rashes.
H2 antihistamines:
Effects- cause a marked reduction in H+ output, pepsin activity, and the total volume of gastric secretion.
Uses of H2: inhibit both basal and stimulate secretion of gastric acid. Used on Gi disorders to relieve reduction of acid secretion may relieve symptoms.
Adverse effects H2- minor symptoms: dizziness, lethargy, and fatigue. More serious- mental confusion, delirium, seizures. Cimetidine has been shown to increase blood concentrations of numerous drugs, including anticoagulation of the warfarin type, TCAs, and various benzodiazepines.
Drugs: pyrilamine (antihistamine), thioperamide (antagonist)